ABSTRACT Background: Small fiber neuropathy (SFN) leads to sensory and autonomic dysfunction by affecting small-diameter myelinated A-delta and unmyelinated C fibers, with vitamin B12 deficiency identified as one of its causes. Objectives: To achieve early diagnosis of SFN in patients with vitamin B12 deficiency and to illustrate the impact of vitamin B12 replacement therapy using noninvasive electrophysiological tests. Materials and Methods: Patients aged 18 to 65 with vitamin B12 deficiency experiencing neuropathic pain or autonomic symptoms were included. A control group consisted of asymptomatic, healthy volunteers with normal B12 levels. Neurological examinations, cutaneous silent period (CSP), sympathetic skin response (SSR), and cardiovascular autonomic tests (R-R interval variability during the Valsalva maneuver [RRIV-VM] and standing [RRIV-S]) were performed at admission and six months later. Patients received 1000 mcg cyanocobalamin intramuscularly daily for one week, weekly for one month, and monthly for three months. Results: The final analyses included 25 patients and 25 controls. At admission, patients had significantly longer CSP and SSR latencies compared to controls (P = 0.047, P < 0.001) and shortened CSP durations (P = 0.043). The SSR amplitude was lower in patients but not significantly (P = 0.823). Post-treatment, CSP latency, CSP duration, and SSR latency significantly improved (P < 0.001, P = 0.002, P < 0.001). Positive symptoms and autonomic symptoms improved significantly after treatment (P = 0.039, P = 0.016). The number of patients with neuropathic pain significantly decreased (P = 0.008). Conclusion: CSP latency, CSP duration, and SSR latency are effective, non-invasive, and cost-effective screening tests for diagnosing SFN in individuals with B12 deficiency. These tests are also valuable for monitoring the progression of SFN following vitamin B12 replacement therapy. The study supports the use of these noninvasive electrophysiological tests to enhance early diagnosis and treatment efficacy in SFN associated with vitamin B12 deficiency.
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